Influence of repeated painful procedures and sucrose analgesia on the development of hyperalgesia in newborn infants

This study determined the effects of cumulative exposure to painful needle procedures and sucrose analgesia on the development of remote hyperalgesia in newborn infants, defined as an increase in response to a normally painful stimulus at a site distal from the site of injury. One-hundred and twenty healthy newborns and 120 healthy newborn infants of diabetic mothers equally randomized to sucrose analgesia or placebo prior to all needle procedures in the first two days after birth were divided into two exposure groups according to number of needle procedures they had undergone [high (5) or low (4)] using the median cut-off technique. Compared to the low exposure group, infants in the high exposure group had a higher pain response during a subsequent venipuncture distal to the site of previous injury, assessed by the Premature Infant Pain Profile (PIPP) [7.1 vs. 8.4; p = 0.012] and Visual Analog Scale (VAS) [2.5 cm vs. 3.2 cm; p = 0.047], and a trend for longer cry duration [25.7 s vs. 33.8 s; p = 0.171]. PIPP scores did not differ during a routine diaper change, suggesting a nociceptive specific mechanism for the remote hyperalgesia to venipuncture. Sucrose reduced PIPP, VAS, and cry duration scores during venipuncture, but did not prevent hyperalgesia (p > 0.05). There was a preponderance of infants of diabetic mothers in the high exposure group; however, the analysis did not demonstrate this to be a confounding factor. In conclusion, sucrose analgesia for repeated painful procedures in the first day of life does not prevent development of remote hyperalgesia in newborns.